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Nishioka et al. Hepatoma Res 2018;4:1  I  http://dx.doi.org/10.20517/2394-5079.2017.46                                             Page 7 of 12



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               Figure 2. Profile of the running enrichment score and position of gene set members on the rank ordered list for (A) MYC_TARGETS_V1;
               (B) MYC_TARGETS_V2; and (C) UNFOLDED_PROTEIN_RESPONSE from the HALLMARKS gene set collection. The two MYC_TARGETS
               gene sets (comprised of 200 and 58 genes, respectively) share only 18 genes in common

               these HCC-specific gene sets, 14 gene sets from the CGP collection representing MYC target genes were
               also found to be significantly enriched in the high AFP class, which falls in agreement with the enrichment
               analysis results obtained using the Hallmarks collection. A heat map of the top ranked genes from this
               analysis is shown in Supplementary Figure 2. No significant differences in gene set enrichment were found
               between phenotype classes determined by age, gender, FIB4 or HBV-status using either the Hallmarks or
               CGP collections.

               Survival analysis
               A Kaplan-Meier plot comparing the survival of patients with serum AFP level > 400 ng/mL versus patients
               with lower serum AFP levels is shown in Figure 3A. Serum AFP level > 400 ng/mL was significantly
               associated with poorer overall survival (Log-Rank P = 0.040) and a hazard ratio for mortality of 3.1 (95%CI
               1.0-9.7, P = 0.050).
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